This project examined neuronal and glial cells and interaction/signalling between these cells in nervous system injury. Within the nervous system, regulation of microglia cells in determining neuronal cell death has become a major biological question. In this project we examine a number of events that occur upon injury to the nervous system including the response cascade of microglia activation, astrogliosis, neuronal necrosis and loss. We have demonstrated a spatio-temporal pattern of response for pro-inflammatory cytokines, chemokines, apoptotic factors, and cell-cycle proteins in chemical-induced injury of the mouse hippocampus. Data suggest that cell cycle regulation is critical to the stage specific response of microglia cells in the full pattern of neurodegeneration. The specificity of cell cycle mRNA and TNF receptor mRNA has been determined using laser capture microdissection and immunohistochemical co-localization to distinct neuronal populations with differing cell fates. Future Research is based upon the hypothesis that neurons and microglia progress through various stages of a cell cycle regulatory response and that cell senescence may be related to the macrophage phenotype of the microglia cell in regions of significant neuronal degeneration.